Growth hormone, which is secreted from the pituitary, stimulates growth of all tissues of the body that are capable of growing. In addition, growth hormone is known to have the following basic effects on the metabolic processes of the body:
1. Increased rate of protein synthesis in all cells of the body; PA1 2. Decreased rate of carbohydrate utilization in cells of the body; PA1 3. Increased mobilization of free fatty acids and use of fatty acids for energy. PA1 R.sub.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, and where two C.sub.1 -C.sub.6 alkyl groups are present on one atom, they may be optionally joined to form a C.sub.3 -C.sub.8 cyclic ting optionally including oxygen, sulfur or NR.sub.2a ; PA1 R.sub.2a is hydrogen or C.sub.1 -C.sub.6 alkyl; PA1 R.sub.3a and R.sub.3b are independently hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, OR.sub.2, cyano, OCF.sub.3, methylenedioxy, nitro, S(O).sub.m R, CF.sub.3 or C(O)OR.sub.2, and when R.sub.3a and R.sub.3b are in an ortho arrangement they maybe joined to form a C.sub.5 to C.sub.8 aliphatic or aromatic ring optoinally icluding 1 or 2 heteroatoms selected from oxygen,sulfer, or nitrogen; PA1 R.sub.4 and R.sub.5 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl where the substituents may be 1 to 5 halo, 1 to 3 hydroxy, 1 to 3 C.sub.1 -C.sub.10 alkanoyloxy, 1 to 3 C.sub.1 -C.sub.6 alkoxy, phenyl, phenoxy, 2-furyl, C.sub.1 -C.sub.6 alkoxycarbonyl, S(O).sub.m (C.sub.1 -C.sub.6 alkyl); or R.sub.4 and R.sub.5 can be taken together to form --(CH.sub.2).sub.r L.sub.a (CH.sub.2).sub.S -- where L.sub.a is C(R.sub.2).sub.2, O, S(O).sub.m or N(R.sub.2), r and s are independently 1 to 3 and R.sub.2 is as defined above; PA1 R.sub.6 is hydrogen or C.sub.1 -C.sub.6 alkyl; PA1 A is: ##STR2## where x and y are independently 0-3; Z is N--R.sub.2 or O; PA1 R.sub.7 and R.sub.7a are independently hydrogen, C.sub.1 -C.sub.6 alkyl, trifluoromethyl, phenyl, substituted C.sub.1 -C.sub.6 alkyl where the substituents are imidazolyl, phenyl, indolyl, p-hydroxyphenyl, OR.sub.2, S(O).sub.m R.sub.2, C(O)OR.sub.2, C.sub.3 -C.sub.7 cycloalkyl, N(R.sub.2)(R.sub.2), C(O)N(R.sub.2)(R.sub.2); or R.sub.7 and R.sub.7a can independently be joined to one or both of R.sub.4 and R.sub.5 groups to form alkylene bridges between the terminal nitrogen and the alkyl portion of the R.sub.7 or R.sub.7a groups, wherein the bridge contains 1 to 5 carbons atoms; PA1 B, D, E, and F are independently C(R.sub.8)(R.sub.10), or C.dbd.O, such that one or two of B,D,E, or F may be optionally missing to provide a 5, 6, or 7 membered ring; or B and D or D and E taken together may be CR.sub.8 .dbd.CR.sub.10, where CR.sub.8 .dbd.CR.sub.10 may include a benzofusion in which R.sub.8 and R.sub.10 ethylene units are linked to form a phenyl ring; PA1 R.sub.8 and R.sub.10 are independently hydrogen, R.sub.2, (CH.sub.2).sub.q aryl, (CH.sub.2).sub.q O(R.sub.2), (CH.sub.2).sub.q O(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q OC(O)R.sub.2, (CH.sub.2).sub.q OC(O)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q OC(O)N(R.sub.2)(R.sub.2), (CH.sub.2).sub.q OC(O)N(R.sub.2)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q C(O)R.sub.2, (CH.sub.2).sub.q C(O)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q C(O)OR.sub.2, (CH.sub.2).sub.q C(O)O(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q C(O)N(R.sub.2)(R.sub.2), (CH.sub.2).sub.q C(O)N(R.sub.2)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q N(R.sub.2)(R.sub.2), (CH.sub.2).sub.q N(R.sub.2)(R.sub.9), (CH.sub.2).sub.q S(O).sub.m R.sub.2, (CH.sub.2).sub.q S(O).sub.m (CH.sub.2).sub.t aryl, (CH.sub.2).sub.q SO.sub.2 N(R.sub.2)(R.sub.2), (CH.sub.2).sub.q SO.sub.2 N(R.sub.2)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q (1H-tetrazol-5-yl), (CH.sub.2).sub.q C(O)NHSO.sub.2 R.sub.2, (CH.sub.2).sub.q C(O)NHSO.sub.2 (CH.sub.2).sub.t aryl, (CH.sub.2).sub.q SO.sub.2 NHC(O)R.sub.2, (CH.sub.2).sub.q SO.sub.2 NHC(O)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q SO.sub.2 NH(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q SO.sub.2 NH--C.tbd.N and the (CH.sub.2).sub.t may be substituted by 1 to 2 C.sub.1-4 alkyl and the R.sub.2, (CH.sub.2).sub.q and aryl groups may optionally be substituted by 1 to 5 halogen, 1 to 30R.sub.2a, C(O)OR.sub.2a, C(O)O(CH.sub.2).sub.t aryl, 1 to 3 C.sub.1 -C.sub.4 alkyl, C(O)N(R.sub.2a)(R.sub.2a), SO.sub.2 N(R.sub.2a)(R.sub.2a), S(O).sub.m R.sub.2a, N(R.sub.2a)(R.sub.2a), 1 to 2 CF.sub.3, or 1H-tetrazol-5-yl; PA1 R.sub.9 is R.sub.2, (CH.sub.2).sub.q aryl, C(O)R.sub.2, C(O)(CH.sub.2).sub.t aryl, C(O)N(R.sub.2)(R.sub.2), C(O)N(R.sub.2)(CH.sub.2).sub.t aryl, C(O)OR.sub.2, C(O)O(CH.sub.2).sub.t aryl, S(O).sub.2 N(R.sub.2)(R.sub.2), SO.sub.2 N(R.sub.2)(CH.sub.2).sub.t aryl, SO.sub.2 R.sub.2 or SO.sub.2 (CH.sub.2).sub.t aryl and the (CH.sub.2).sub.t may be substituted by 1 to 2 C.sub.1 -C.sub.4 alkyl and the R.sub.2, (CH.sub.2).sub.q and aryl groups may optionally be substituted by 1 to 5 halogen, 1 to 3 OR.sub.2a, C(O)OR.sub.2a, C(O)O(CH.sub.2).sub.t aryl, 1 to 3 C.sub.1 -C.sub.4 alkyl, C(O)N(R.sub.2a)(R.sub.2a), SO.sub.2 N(R.sub.2a)(R.sub.2a), S(O).sub.m R.sub.2a, N(R.sub.2a)(R.sub.2a) or 1 to 2 CF.sub.3. PA1 m is 0 to 2; PA1 n is 1 or 2; PA1 q is 0 to 3; PA1 t is 0 to 3; and PA1 G, H, I and J are carbon, nitrogen, sulfur or oxygen atoms, such that at least one is a heteroatom and one of G, H, I or J may be optionally missing to afford 5 or 6 membered heterocyclic aromatic rings; and pharmaceutically acceptable salts and individual diastereomers thereof. PA1 R.sub.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, and, if two C.sub.1 -C.sub.6 alkyl groups are present on one atom, they may be optionally joined to form a C.sub.4 -C.sub.6 cyclic ting optionally including oxygen, sulfur or NR.sub.2a ; PA1 R.sub.2a is hydrogen or C.sub.1 -C.sub.6 alkyl; PA1 R.sub.3a and R.sub.3b are independently hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, OR.sub.2, methylenedioxy, nitro, S(O).sub.m C.sub.1 -C.sub.4 alkyl, CF.sub.3 or C(O)OR.sub.2 ; PA1 R.sub.4 and R.sub.5 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl where the substituents may be 1 to 5 halo, 1 to 2 hydroxy, 1 to 2 C.sub.1 -C.sub.6 alkanoyloxy, 1 to 2 C.sub.1 -C.sub.6 alkyloxy or S(O).sub.m (C.sub.1 -C.sub.4 alkyl); PA1 A is: ##STR4## where x and y are independently 0-3; R.sub.7 and R.sub.7 a are independently hydrogen, C.sub.1 -C.sub.4 alkyl, substituted C.sub.1 -C.sub.4 alkyl where the substituents are from 1 to 3 fluoro or imidazolyl, phenyl, indolyl, S(O).sub.m C.sub.1 -C.sub.4 alkyl, C(O)OR.sub.2 or R.sub.7 and R.sub.7a can independently be joined to one or both of the R.sub.4 and R.sub.5 groups to form alkylene bridges between the terminal nitrogen and the alkyl portion of the R.sub.7 or R.sub.7a groups, wherein the bridges contains 1 to 3 carbon atoms; PA1 B, D and F are independently C(R.sub.8)(R.sub.10) or C.dbd.O, such that one of B, D or F may be optionally missing to provide a 5 or 6 membered ring; or B and D taken together may be CR.sub.8 .dbd.CR.sub.10 and CR.sub.8 .dbd.CR.sub.10 may include a benzofusion in which R.sub.8 and R.sub.10 ethylene units are linked to form a phenyl ring; PA1 R.sub.8 and R.sub.10 are independently hydrogen, R.sub.2, (CH.sub.2).sub.q aryl, (CH.sub.2).sub.q OR.sub.2, (CH.sub.2).sub.q O(CH.sub.2).sub.t aryl (CH.sub.2).sub.q OC(O)R.sub.2, (CH.sub.2).sub.q C(O)OR.sub.2, (CH.sub.2).sub.q C(O)O(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q C(O)N(R.sub.2)(R.sub.2), (CH.sub.2).sub.q C(O)N(R.sub.2)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q N(R.sub.2)C(O)R.sub.2, (CH.sub.2).sub.q N(R.sub.2)C(O)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q N(R.sub.2)C(O)N(R.sub.2)(R.sub.2), (CH.sub.2).sub.q N(R.sub.2)C(O)N(R.sub.2)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q N(R.sub.2)SO.sub.2 R.sub.2, (CH.sub.2).sub.q N(R.sub.2)SO.sub.2 (CH.sub.2).sub.t aryl, (CH.sub.2).sub.q S(O).sub.m R.sub.2, (CH.sub.2).sub.q S(O).sub.m (CH.sub.2).sub.t aryl, (CH.sub.2).sub.q S(O).sub.m N(H)CN, (CH.sub.2).sub.q (1H-tetrazol-5-yl), (CH.sub.2).sub.q C(O)NHSO.sub.2 R.sub.2, (CH.sub.2).sub.q C(O)NHSO.sub.2 (CH.sub.2).sub.t aryl, (CH.sub.2).sub.q SO.sub.2 NH(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q SO.sub.2 NHC(O)R.sub.2, (CH.sub.2).sub.q SO.sub.2 NHC(O)CH.sub.2).sub.t aryl and the (CH.sub.2).sub.t and (CH.sub.2).sub.q may be substituted by 1 to 2 C.sub.1 -C.sub.2 alkyl and the R.sub.2 and aryl groups may optionally be substituted by 1 to 2 halogens, OR.sub.2a, C(O)OR.sub.2a,C(O)O(CH.sub.2).sub.t aryl, S(O).sub.m C.sub.1 -C.sub.4 alkyl, 1 to 2 C.sub.1 -C.sub.3 alkyl or 1H-tetrazol-5-yl; PA1 m is 0 to 2; PA1 q is 0 to 3; PA1 t is 0 to 3; and PA1 the aryl group is phenyl, napthyl,pyridyl, thienyl, furanyl, indolyl, N-methyl indolyl, thiazolyl, or pyrimidinyl and the pharmaceutically acceptable salts and individual diasteromers thereof. PA1 R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, and, if two C.sub.1 -C.sub.4 alkyls are present on one atom, they may be optionally joined to form a C.sub.5 -C.sub.6 cyclic ring optionally including oxygen or NR.sub.2a ; PA1 R.sub.2a is hydrogen or C.sub.1 -C.sub.4 alkyl; PA1 R.sub.3a and R.sub.3b are independently hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, hydroxy, C(O)OR.sub.2, hydroxy, C.sub.1 -C.sub.4 alkoxy, S(O).sub.m C.sub.1 -C.sub.4 alkyl or CF.sub.3 ; PA1 R.sub.4 and R.sub.5 are independently hydrogen, C.sub.1 -C.sub.4 alkyl, substituted C.sub.1 -C.sub.4 alkyl where the substituents may be 1 to 2 hydroxy or S(O).sub.m (C.sub.1 -C.sub.3 alkyl); ##STR6## where x is 0 or 1; R.sub.7 and R.sub.7a are independently hydrogen, C.sub.1 -C.sub.3 alkyl; or R.sub.7 and R.sub.7a can independently be joined to one or both of the R.sub.4 and R.sub.5 groups to form alkylene bridges between the terminal nitrogen and the alkyl portion of the R.sub.7 or R.sub.7a groups to form 5 or 6 membered rings containing the terminal nitrogen; PA1 B and D are independently C(R.sub.8)(R.sub.10), C.dbd.O, or B and D taken together may be CR.sub.8 .dbd.CR.sub.10 ; PA1 R.sub.8 and R.sub.10 are independently hydrogen, R.sub.2, (CH.sub.2).sub.q aryl, (CH.sub.2).sub.q OR.sub.2, (CH.sub.2).sub.q O(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q OC(O)R.sub.2, (CH.sub.2).sub.q C(O)OR.sub.2, (CH.sub.2).sub.q C(O)O(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q C(O)N(R.sub.2)(R.sub.2), (CH.sub.2).sub.q C(O)N(R.sub.2)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q N(R.sub.2)C(O)R.sub.2, (CH.sub.2).sub.q N(R.sub.2)C(O)(CH.sub.2).sub.t aryl,(CH.sub.2).sub.q N(R.sub.2)C(O)N(R.sub.2)(R.sub.2), (CH.sub.2).sub.q N(R.sub.2)C(O)N(R.sub.2)(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q N(R.sub.2)SO.sub.2 R.sub.2, (CH.sub.2).sub.q N(R.sub.2)SO.sub.2 (CH.sub.2).sub.t aryl, (CH.sub.2).sub.q S(O).sub.m R.sub.2, (CH.sub.2)q(1H-tetrazol-5-yl), (CH.sub.2).sub.q C(O)NHSO.sub.2 R.sub.2, (CH.sub.2).sub.q C(O)NHSO.sub.2 (CH.sub.2).sub.t aryl, (CH.sub.2).sub.q SO.sub.2 NH(CH.sub.2).sub.t aryl, (CH.sub.2).sub.q SO.sub.2 NHC(O)R.sub.2, (CH.sub.2).sub.q SO.sub.2 NHC(O)CH.sub.2).sub.t aryl and the (CH.sub.2).sub.t and (CH.sub.2).sub.q may be substituted by 1 to 2 C.sub.1 -C.sub.2 alkyl and the R.sub.2 and aryl groups may optionally be substituted by 1 to 2 halogens, OR.sub.2a, C(O)OR.sub.2a, C(O)O(CH.sub.2).sub.t aryl, S(O).sub.m R.sub.2a, 1 to 2 C.sub.1 -C.sub.3 alkyl or 1H-tetrazol-5-yl; PA1 m is 0 to 2; PA1 q is 0 to 2; PA1 t is 0 to 2; and PA1 aryl is phenyl, pyridyl, indolyl, N-methyl indolyl, or pyrimidinyl or thienyl and the pharmaceutically acceptable salts and individual diastereomers thereof. PA1 1. N-[1(R)-[(2,3-Dihydrospiro[1H-indene-1,4'-piperidin]-1'-yl)carbonyl]-2-(1H -indol-3-yl)ethyl]-2-amino-2-methylpropanamide PA1 2. N-[1(RS)-[(2,3-Dihydrospiro[1H-indene-1,4'-piperidin]-1'-yl)carbonyl]-2-(5 -fluoro-1H-indol-3-yl)ethyl]-2-amino-2-methylpropanamide PA1 3. N-[1(RS)-[(2,3-Dihydro-3-oxospiro[1H-indene-1,4'-piperidin]-1'-yl)-carbony l]-2-(1H-indol-3-yl)ethyl]-2-amino-2-methylpropanamide PA1 4. N-[1(RS)-[(2,3-Dihydro-3(RS)-hydroxyspiro[1H-indene-1,4'-piperidin]-1'-yl) carbonyl]-2-(1H-indol-3-yl)ethyl]-2-amino-2-methylpropanamide PA1 5. N-[1(R)-[(2,3-Dihydro-6-fluorospiro[1H-indene-1,4'-piperidin]-1'-yl) carbonyl]-2-(indol-3-yl)ethyl]-2-amino-2-methylpropanamide PA1 6. N-[1(R)-[(2,3-Dihydrospiro[1H-indene-1,4'-piperidin]-1'-yl)carbonyl]-2-(ph enylmethyloxy)ethyl]-2-amino-2-methylpropanamide PA1 7. N-[1(R)-[(2,3-Dihydro-3-oxospiro[1H-indene-1,4'-piperidin]-1'-yl)carbonyl] -2-(phenylmethyloxy)ethyl]-2-amino-2-methylpropanamide PA1 8. N-[1(R)-[(2,3-Dihydro-3(RS)-hydroxyspiro[1H-indene-1,4'-piperidin]-1'-yl) carbonyl]-2-(phenylmethyloxy)ethyl]-2-amino-2-methylpropanamide PA1 9. N-[1(R)-[(2,3-Dihydrospiro[1H-indene-1,4'-piperidin]-1'-yl)carbonyl]-2-(2' ,6'-difluorophenylmethyloxy)ethyl]-2-amino-2-methylpropanamide PA1 10. N-[1(RS)-[(2,3-Dihydro-3(RS)-hydroxyspiro[1H-indene-1,4'-piperidin]-1'-yl) carbonyl]-3-phenylpropyl]-2-amino-2-methylpropanamide PA1 11. N-[1(R)-[(2,3-Dihydro-3-oxospiro[1H-indene-1,4'-piperidin]-1'-yl)carbonyl] -3-cyclohexylpropyl]-2-amino-2-methylpropanamide PA1 12. N-[1(R)-[(2,3-Dihydro-3-(RS)-hydroxyspiro[1H-indene-1,4'-piperidin]-1'-yl) carbonyl]-3-cyclohexylpropyl]-2-amino-2-methylpropanamide PA1 13. N-[1(R)-[(2,3-Dihydro-3-oxospiro[1H-indene-1,4'-piperidin]-1'-yl)carbonyl] -4-phenylbutyl]-2-amino-2-methylpropanamide PA1 14. N-[1(R)-[(2,3-Dihydro-3(RS)-hydroxyspiro[1H-indene-1,4'-piperidin]-1'-yl) carbonyl]-4-phenylbutyl]-2-amino-2-methylpropanamide PA1 15. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl ]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-carboxylic acid; PA1 16. 1'[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl] -2,3-dihydrospiro[1H-indene-1,4'-piperidine-3-carboxylic acid ethyl ester; PA1 17. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3-carboxylic acid; PA1 18. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3-carboxylic acid ethyl ester; PA1 19. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl ]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid; PA1 20. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl ]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3(R)-acetic acid; PA1 21. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl ]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3(S)-acetic acid; PA1 22. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl ]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid ethyl ester; PA1 23. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl ]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3(R)-acetic acid ethyl ester; PA1 24. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl ]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3(S)-acetic acid ethyl ester; PA1 25. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(5-fluoroindole-3-yl)-1-o xopropyl]-2,3-dihydrospiro[1H-indene-1,4-piperidine]-3-acetic acid; PA1 26. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(5-fluoroindole-3-yl)-1-o xopropyl]-2,3-dihydrospiro[1H-indene-1,4-piperidine]-3(R)-acetic acid; PA1 27. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(5-fluoroindole-3-yl)-1-o xopropyl]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3(S)-acetic acid; PA1 28. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(5-fluoroindole-3-yl)-1-o xopropyl]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid ethyl ester; PA1 29. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(5-fluoroindole-3-yl)-1-o xopropyl]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3(R)-acetic acid ethyl ester; PA1 30. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(5-fluoroindole-3-yl)-1-o xopropyl]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3(S)-acetic acid ethyl ester; PA1 31. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]3-(phenylmethoxy)-1-oxopropy l]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid; PA1 32. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(phenylmethoxy)-1-oxoprop yl]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid ethyl ester; PA1 33. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(2,6-difluorophenylmethox y)-1-oxopropyl]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid; PA1 34. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(2,6-difluorophenylmethox y)-1-oxopropyl]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid ethyl ester; PA1 35. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(5-fluoroindole-3-yl)-1-o xopropyl]-2,3-dihydro-6-fluorospiro[1H-indene-1,4'-piperidine]-3-acetic acid; PA1 36. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(5-fluoroindole-3-yl)-1-o xopropyl]-2,3-dihydro-6-fluorospiro[1H-indene-1,4'-piperidine]-3-acetic acid ethyl ester; PA1 37. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3-propanoic acid; PA1 38. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3-propionic acid ethyl ester; PA1 39. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid; PA1 40. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3(S)-acetic acid; PA1 41. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine ]-3(R)-acetic acid; PA1 42. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3-acetic acid ethyl ester; PA1 43. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3(S)-acetic acid ethyl ester; PA1 44. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3(R)-acetic acid ethyl ester; PA1 45. N-Ethyl-1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopenty l]-2,3-dihydrospiro[1H-indene-1,4'-piperidine]-3-acetamide; PA1 46. N-Ethyl-1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopenty l]-2,3-dihydrospiro[1H-indene-1,4'-piperidine ]-3(S)-acetamide; PA1 47. N-Ethyl-1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopenty l]-2,3-dihydrospiro[1H-indene-1,4'-piperidine ]-3-acetamide; PA1 48. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydro-6-fluorospiro[1H-indene-1,4'-piperidine]-3-acetic acid; PA1 49. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl-2,3-di hydro-6-fluorospiro[1H-indene-1,4'-piperidine]-3-acetic acid ethyl ester; PA1 50. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3-propanoic acid; PA1 51. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-5-phenyl-1-oxopentyl]-2,3-d ihydrospiro[1H-indene-1,4'-piperidine]-3-propanoic acid ethyl ester; PA1 52. 1'-[2(R)-[(2-amino-2-methyl-1-oxopropyl)amino]-3-(indole-3-yl)-1-oxopropyl ]-2,3-dihydro-6-fluorospiro[1H-indene-1,4'-piperidine]-3-acetic acid.
A deficiency in growth hormone secretion can result in various medical disorders, such as dwarfism.
Various ways are known to release growth hormone. For example, chemicals such as arginine, L-3,4-dihydroxyphenylalanine (L-DOPA), glucagon, vasopressin, and insulin induced hypoglycemia, as well as activities such as sleep and exercise, indirectly cause growth s hormone to be released from the pituitary by acting in some fashion on the hypothalamus perhaps either to decrease somatostatin secretion or to increase the secretion of the known secretagogue growth hormone releasing factor (GRF) or an unknown endogenous growth hormone-releasing hormone or all of these.
In cases where increased levels of growth hormone were desired, the problem was generally solved by providing exogenous growth hormone or by administering GRF or a peptidal compound which stimulated growth hormone production and/or release. In either case the peptidyl nature of the compound necessitated that it be administered by injection. Initially the source of growth hormone was the extraction of the pituitary glands of cadavers. This resulted in a very expensive product and carded with it the risk that a disease associated with the source of the pituitary gland could be transmitted to the recipient of the growth hormone. Recently, recombinant growth hormone has become available which, while no longer carrying any risk of disease transmission, is still a very expensive product which must be given by injection or by a nasal spray.
Other compounds have been developed which stimulate the release of endogenous growth hormone such as analogous peptidyl compounds related to GRF or the peptides of U.S. Pat. No. 4,411,890. These peptides, while considerably smaller than growth hormones are still susceptible to various proteases. As with most peptides, their potential for oral bioavailability is low. The instant compounds are non-peptide analogs for promoting the release of growth hormone which are stable in a variety of physiological environments and which may be administered parenterally, nasally or by the oral route.